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Influenza polymerase

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https://www.readbyqxmd.com/read/28646802/dampness-can-promote-the-influenza-a-virus-and-worsen-its-prognosis-by-upregulating-the-tlr7-signaling-pathway
#1
Deng Li, Xu Huachong, Pang Peng, Zheng Ke, Nie Jiao, Wu Xianlin, Yu Bin, Chen Jia, Chen Xiaoyin
Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646652/influenza-a-virus-cap-snatches-host-rnas-based-on-their-abundance-early-after-infection
#2
Dorota Sikora, Lynda Rocheleau, Earl G Brown, Martin Pelchat
The influenza A virus RNA polymerase cleaves the 5' ends of host RNAs and uses these RNA fragments as primers for viral mRNA synthesis. We performed deep sequencing of the 5' host-derived ends of the eight viral mRNAs of influenza A/Puerto Rico/8/1934 (H1N1) virus in infected A549 cells, and compared the population to those of A/Hong Kong/1/1968 (H3N2) and A/WSN/1933 (H1N1). In the three strains, the viral RNAs target different populations of host RNAs. Host RNAs are cap-snatched based on their abundance, and we found that RNAs encoding proteins involved in metabolism are overrepresented in the cap-snatched populations...
June 21, 2017: Virology
https://www.readbyqxmd.com/read/28639594/viral-aetiology-of-wheezing-in-children-under-five
#3
Prithi Sureka Mummidi, Radha Tripathy, Bhagirathi Dwibedi, Amarendra Mahapatra, Suryakanta Baraha
BACKGROUND & OBJECTIVES: Wheezing is a common problem in children under five with acute respiratory infections (ARIs). Viruses are known to be responsible for a considerable proportion of ARIs in children. This study was undertaken to know the viral aetiology of wheezing among the children less than five years of age, admitted to a tertiary care hospital in eastern India. METHODS: Seventy five children, under the age of five years admitted with wheezing, were included in the study...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28637755/seasonal-h3n2-and-2009-pandemic-h1n1-influenza-a-viruses-reassort-efficiently-but-produce-attenuated-progeny
#4
Kara L Phipps, Nicolle Marshall, Hui Tao, Shamika Danzy, Nina Onuoha, John Steel, Anice C Lowen
Reassortment of gene segments between co-infecting influenza A viruses (IAV) facilitates viral diversification and has significant epidemiological impact on seasonal and pandemic influenza. Since 1977, human IAVs of H1N1 and H3N2 subtypes have co-circulated with relatively few documented cases of reassortment. We evaluated the potential for viruses of the 2009 pandemic H1N1 (pH1N1) and seasonal H3N2 lineages to reassort under experimental conditions. Results of heterologous co-infections with pH1N1 and H3N2 viruses were compared to those obtained following co-infection with homologous, genetically tagged, pH1N1 viruses as a control...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28636855/efficacy-of-recombinant-influenza-vaccine-in-adults-50-years-of-age-or-older
#5
Lisa M Dunkle, Ruvim Izikson, Peter Patriarca, Karen L Goldenthal, Derek Muse, Janice Callahan, Manon M J Cox
BACKGROUND: Improved influenza vaccines are needed to control seasonal epidemics. This trial compared the protective efficacy in older adults of a quadrivalent, recombinant influenza vaccine (RIV4) with a standard-dose, egg-grown, quadrivalent, inactivated influenza vaccine (IIV4) during the A/H3N2-predominant 2014-2015 influenza season, when antigenic mismatch between circulating and vaccine influenza strains resulted in the reduced effectiveness of many licensed vaccines. METHODS: We conducted a randomized, double-blind, multicenter trial of RIV4 (45 μg of recombinant hemagglutinin [HA] per strain, 180 μg of protein per dose) versus standard-dose IIV4 (15 μg of HA per strain, 60 μg of protein per dose) to compare the relative vaccine efficacy against reverse-transcriptase polymerase-chain-reaction (RT-PCR)-confirmed, protocol-defined, influenza-like illness caused by any influenza strain starting 14 days or more after vaccination in adults who were 50 years of age or older...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28631174/studies-of-the-interaction-of-influenza-virus-rna-polymerase-pan-with-endonuclease-inhibitors
#6
Li-Hua Dong, Xiao-Rong Cao
Influenza virus is a major causative agent of respiratory viral infections, and RNA polymerase catalyzes its replication and transcription activities in infected cell nuclei. Since it is highly conserved in all virus strains, RNA polymerase becomes a key target of anti-influenza virus agents. Although experimental studies have revealed the good inhibitory activity of endonuclease inhibitors to RNA polymerase, the mechanism is still unclear. In this study, the docking and molecular dynamics simulations have been performed to explore the interaction of three kinds of endonuclease inhibitors with the subunit (PAN) of RNA polymerase...
June 19, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28629986/identification-of-influenza-polymerase-inhibitors-targeting-polymerase-pb2-cap-binding-domain-through-virtual-screening
#7
Ming Liu, Edwin Chun-Yeung Lo, Guoxin Wang, Hak-Fun Chow, Jacky Chi-Ki Ngo, David Chi-Cheong Wan, Leo Lit-Man Poon, Pang-Chui Shaw
Influenza A virus is the major cause of epidemics and pandemics worldwide. In this study, virtual screening was used to identify compounds interacting with influenza A polymerase PB2 cap-binding domain (CBD). With a database of 21,351 small molecules, 28 candidate compounds were obtained and four of them (225, 225D1, 426 and 426Br) were found to bind directly to PB2 CBD by surface plasmon resonance (SPR). The evaluation of compounds 426Br and 225 indicated that they could bind to PB2 CBD and inhibit influenza virus at low micromolar concentration...
June 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28629724/in-vitro-antiviral-effects-of-peganum-harmala-seed-extract-and-its-total-alkaloids-against-influenza-virus
#8
Mohammad-Taghi Moradi, Ali Karimi, Mahmoud Rafieian-Kopaei, Fatemeh Fotouhi
This research was aimed to evaluate the in vitro antiviral effect and the mechanism of the effect of Peganum. harmala seeds extract against influenza A virus infection using Madin-Darby canine kidney (MDCK) cells. In this research, ethyl alcohol extract of P. harmala seeds and its total alkaloids was prepared. The potential antiviral activity of the extract and its total alkaloids against influenza A/Puerto Rico/8/34 (H1N1; PR8) virus was assessed. The mode of action of the extract to inhibit influenza replication was investigated using virucidal activity, hemagglutination inhibition assay, time of addition assays, RNA replication, western blot analysis and RNA polymerase blocking assay...
June 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28628827/evolutionary-conservation-of-influenza-a-pb2-sequences-reveals-potential-target-sites-for-small-molecule-inhibitors
#9
Hershna Patel, Andreas Kukol
The influenza A basic polymerase protein 2 (PB2) functions as part of a heterotrimer to replicate the viral RNA genome. To investigate novel PB2 antiviral target sites, this work identified evolutionary conserved regions across the PB2 protein sequence amongst all sub-types and hosts, as well as ligand binding hot spots which overlap with highly conserved areas. Fifteen binding sites were predicted in different PB2 domains; some of which reside in areas of unknown function. Virtual screening of ~50,000 drug-like compounds showed binding affinities of up to -10...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28627657/shrna%C3%A2-mediated-np-knockdown-inhibits-the-apoptosis-of-cardiomyocytes-induced-by-h1n1pdm2009-influenza-virus
#10
Kun Yu, Yi Ren, Xiwen Zhang, Taiping Qiao, Zhiguo Liu, Jianhua Shi, Yingnan Wang
Acute influenza-associated myocarditis varies in clinical severity ranging between asymptomatic and fulminant varieties. The most severe cases can result in impaired cardiac function‑associated mortality; however, the mechanism underlying the development of viral myocarditis has yet to be fully elucidated. The present study investigated the apoptosis induced in H9C2 cardiomyocytes by infection with the H1N1pdm2009 virus. The H9C2 cells were transfected with nucleoprotein (NP)‑specific short hairpin (sh) RNA, and viral replication was re‑evaluated in H9C2 cells infected with the H1N1pdm2009 virus, as was the apoptosis induced by the virus...
June 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28622865/pa-x-protein-decreases-replication-and-pathogenicity-of-swine-influenza-virus-in-cultured-cells-and-mouse-models
#11
Xiao-Qian Gong, Ying-Feng Sun, Bao-Yang Ruan, Xiao-Min Liu, Qi Wang, Hai-Ming Yang, Shuai-Yong Wang, Peng Zhang, Xiu-Hui Wang, Tong-Ling Shan, Wu Tong, Yan-Jun Zhou, Guo-Xin Li, Hao Zheng, Guang-Zhi Tong, Hai Yu
Swine influenza viruses have been circulating in pigs throughout world and might be potential threats to human health. PA-X protein is a newly discovered protein produced from the PA gene by ribosomal frameshifting and the effects of PA-X on the 1918 H1N1, the pandemic 2009 H1N1, the highly pathogenic avian H5N1 and the avian H9N2 influenza viruses have been reported. However, the role of PA-X in the pathogenesis of swine influenza virus is still unknown. In this study, we rescued the H1N1 wild-type (WT) classical swine influenza virus (A/Swine/Guangdong/1/2011 (H1N1)) and H1N1 PA-X deficient virus containing mutations at the frameshift motif, and compared their replication properties and pathogenicity of swine influenza virus in vitro and in vivo...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28622854/linear-dna-vaccine-prepared-by-large-scale-pcr-provides-protective-immunity-against-h1n1-influenza-virus-infection-in-mice
#12
Fei Wang, Quanjiao Chen, Shuntang Li, Chenyao Zhang, Shanshan Li, Min Liu, Kun Mei, Chunhua Li, Lixin Ma, Xiaolan Yu
Linear DNA vaccines provide effective vaccination. However, their application is limited by high cost and small scale of the conventional polymerase chain reaction (PCR) generally used to obtain sufficient amounts of DNA effective against epidemic diseases. In this study, a two-step, large-scale PCR was established using a low-cost DNA polymerase, RKOD, expressed in Pichia pastoris. Two linear DNA vaccines encoding influenza H1N1 hemagglutinin (HA) 1, LEC-HA, and PTO-LEC-HA (with phosphorothioate-modified primers), were produced by the two-step PCR...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28619132/co-infection-of-h9n2-subtype-avian-influenza-virus-and-infectious-bronchitis-virus-decreases-sp-a-expression-level-in-chickens
#13
Qi Huang, Kai Wang, Ling Pan, Kezong Qi, Hongmei Liu, Hongjun Chen
Chicken surfactant protein A (cSP-A) is a collectin believed to play an important role in antiviral immunity. However, cSP-A expression in the respiratory tract of chickens after viral co-infection remains unclear. The aim of this study was the detection and characterization of cSP-A in co-infected chickens. For this purpose, four-week-old specific pathogen-free (SPF) chickens were divided into five groups and inoculated intranasally with H9N2 subtype avian influenza virus (AIV), infectious bronchitis virus (IBV), or Newcastle disease virus (NDV)...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28615935/serum-inflammatory-biomarkers-and-clinical-outcomes-of-copd-exacerbation-caused-by-different-pathogens
#14
Theerasuk Kawamatawong, Apitch Apiwattanaporn, Warisara Siricharoonwong
BACKGROUND AND OBJECTIVE: COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment. Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation. We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens. METHODS: COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28611246/inhibition-of-avian-influenza-a-virus-replication-in-human-cells-by-host-restriction-factor-tufm-is-correlated-with-autophagy
#15
Shu-Ming Kuo, Chi-Jene Chen, Shih-Cheng Chang, Tzu-Jou Liu, Yi-Hsiang Chen, Sheng-Yu Huang, Shin-Ru Shih
Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2627E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2627K (human signature) and PB2627E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2627E than PB2627K in transfected human cells...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28606367/assessment-of-hygienic-conditions-of-live-bird-markets-on-avian-influenza-in-chittagong-metro-bangladesh
#16
Md Abu Sayeed, Casey Smallwood, Tasneem Imam, Rashed Mahmud, Rubyath Binte Hasan, Mahmudul Hasan, M Sawkat Anwer, Md Harun Rashid, Md Ahasanul Hoque
Live Bird Markets (LBMs) in Asian countries are considered as hubs for the spread and maintenance of different infectious diseases. In Bangladesh, LBMs are the major source of live and dressed poultry to consumers and until now only a few studies have been conducted targeting infectious agent status such as avian influenza virus (AIV) prevalence of LBMs in Bangladesh. Therefore, a cross sectional study was conducted using all 40 LBMs within the Chittagong Metropolitan Area (CMA) of Bangladesh targeting demographic information and hygienic status of LBMs in concurrence with AIV prevalence and its subtype distribution, as well as the associated risk factors for AIV...
July 1, 2017: Preventive Veterinary Medicine
https://www.readbyqxmd.com/read/28605562/microorganisms-associated-with-pneumonia-in-children-5-years-of-age-in-developing-and-emerging-countries-the-gabriel-pneumonia-multicenter-prospective-case-control-study
#17
Thomas Bénet, Valentina Sánchez Picot, Mélina Messaoudi, Monidarin Chou, Tekchheng Eap, Jianwei Wang, Kunling Shen, Jean-William Pape, Vanessa Rouzier, Shally Awasthi, Nitin Pandey, Ashish Bavdekar, Sonali Sanghavi, Annick Robinson, Mala Rakoto-Andrianarivelo, Maryam Sylla, Souleymane Diallo, Pagbajabyn Nymadawa, Nymadawaagiin Naranbat, Graciela Russomando, Wilma Basualdo, Florence Komurian-Pradel, Hubert Endtz, Philippe Vanhems, Gláucia Paranhos-Baccalà
Background.: Pneumonia, the leading infectious cause of child mortality globally, mainly afflicts developing countries. This prospective observational study aimed to assess the microorganisms associated with pneumonia in children aged <5 years in developing and emerging countries. Methods.: A multicenter, case-control study by the GABRIEL (Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries) network was conducted between 2010 and 2014 in Cambodia, China, Haiti, India (2 sites), Madagascar, Mali, Mongolia, and Paraguay...
June 12, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28597818/enhanced-pathogenicity-and-neurotropism-of-mouse-adapted-h10n7-influenza-virus-are-mediated-by-novel-pb2-and-na-mutations
#18
Xuxiao Zhang, Guanlong Xu, Chenxi Wang, Ming Jiang, Weihua Gao, Mingyang Wang, Honglei Sun, Yipeng Sun, Kin-Chow Chang, Jinhua Liu, Juan Pu
The H10 subtype of avian influenza viruses (AIVs) circulates globally in wild birds and poultry, and this subtype has been shown to be increasingly prevalent in China. Among the various H10 viruses, H10N7 AIVs have caused repeated mammal and human infections. To investigate their genetic adaptation in mammals, we generated a mouse-adapted avian H10N7 variant (A/mallard/Beijing/27/2011-MA; BJ27-MA) which exhibited increased virulence in mice compared to wild-type virus and acquired neurotropism. Sequencing showed the absence of the widely recognized mammalian adaptation markers of E627K and D701N in PB2 in the mouse-adapted strain; instead, five amino acid mutations were identified: E158G and M631L in PB2; G218E in haemagglutinin (H3 numbering); and K110E and S453I in neuraminidase (NA)...
June 8, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28579769/ampicillin-resistance-in-haemophilus-influenzae-from-copd-patients-in-the-uk
#19
Satyanarayana Maddi, Umme Kolsum, Sarah Jackson, Richard Barraclough, Barbara Maschera, Karen D Simpson, Thierry G Pascal, Serge Durviaux, Edith M Hessel, Dave Singh
BACKGROUND: Haemophilus influenzae is commonly isolated from the airways of COPD patients. Antibiotic treatment may cause the emergence of resistant H. influenzae strains, particularly ampicillin-resistant strains, including β-lactamase-negative ampicillin resistance (BLNAR) strains. Genetic identification using ftsI sequencing is the optimum method for identifying mutations within BLNAR strains. The prevalence of BLNAR in COPD patients during the stable state has not been reported. We investigated the antibiotic resistance patterns of H...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28575367/colonization-density-of-the-upper-respiratory-tract-as-a-predictor-of-pneumonia-haemophilus-influenzae-moraxella-catarrhalis-staphylococcus-aureus-and-pneumocystis-jirovecii
#20
Daniel E Park, Henry C Baggett, Stephen R C Howie, Qiyuan Shi, Nora L Watson, W Abdullah Brooks, Maria Deloria Knoll, Laura L Hammitt, Karen L Kotloff, Orin S Levine, Shabir A Madhi, David R Murdoch, Katherine L O'Brien, J Anthony G Scott, Donald M Thea, Dilruba Ahmed, Martin Antonio, Vicky L Baillie, Andrea N DeLuca, Amanda J Driscoll, Wei Fu, Caroline W Gitahi, Emmanuel Olutunde, Melissa M Higdon, Lokman Hossain, Ruth A Karron, Abdoul Aziz Maiga, Susan A Maloney, David P Moore, Susan C Morpeth, John Mwaba, Musaku Mwenechanya, Christine Prosperi, Mamadou Sylla, Somsak Thamthitiwat, Scott L Zeger, Daniel R Feikin
Background.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. Methods.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR)...
June 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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